目的 阐明盐酸青藤碱（SIN-HCl）挥发油边缘活化PEG修饰传递体（SHPT）的经皮吸收特性，并与其他载体进行对比研究。方法 采用乙醇注入法制备不同处方的传递体[SHPT不同挥发油用量的3个代表性处方SHPT-A、SHPT-B、SHPT-C，SHPT-A、SHPT-B分别对应的非PEG修饰传递体（SHT-A、SHT-B），脱氧胆酸钠（DOC）边缘活化的传递体（SHDT）]、PEG修饰脂质体（SHPL）和脂质体（SHLS），对其粒径、形态、弹性和包封率等理化性质进行表征，其中弹性以恒定压力挤出法测定，包封率以HPLC结合离心超滤法测定；采用Franz扩散池评价载体的离体皮肤渗透特性，考察不同载体类型（SHPT、SHDT、SHLS和SIN-HCl水溶液）及SHPT处方中二硬脂酰基磷脂酰乙醇胺-聚乙二醇（DSPE-PEG）2000、挥发油对药物经皮渗透的影响。结果 SIN-HCl传递体和脂质体均为近似圆形的单层囊泡，平均粒径在93～118 nm，无聚集现象，其包封率在11%～40%。囊泡弹性大小顺序为SHPT-B >SHDT≈SHPT-A >SHT-B >SHT-A≈SHPL >SHLS >SHPT-C。药物稳态经皮渗透速率[J，μg/(cm²·h)]大小顺序为SHT-B（19.10±5.74） >SHPT-B（17.06±0.34） >SHDT（15.16±0.55） >SHT-A（10.96±0.99） >SHPT-A（9.42±1.09） >SHLS（3.90±0.67） >SHPT-C（3.51±0.37） >SIN-HCl水溶液（2.26±0.94）。SHT-B、SHPT-B、SHDT、SHLS、SHPT-C及SIN-HCl水溶液36 h的累积透过率（Q_e）分别为（89.79±6.67）%、（84.01±6.77）%、（73.98±10.55）%、（20.29±3.21）%、（15.45±3.04）%和（10.33±2.91）%。与SHLS和SIN-HCl水溶液的时滞（T_lag）（3.5～3.8 h）相比，SHPT-A、SHPT-B及其对应的非PEG修饰传递体与SHDT呈现较短的Tlag（0.3～0.6 h）。结论 合适用量的挥发油边缘活化的SIN-HCl PEG修饰传递体具有良好的弹性和离体皮肤渗透特性，并在不同程度上优于DOC边缘活化的传递体和普通脂质体。

Objective To clarify the percutaneous absorption characteristics of sinomenine hydrochloride (SIN-HCl) PEGylated transfersomes (SHPT) edge activated by volatile oils and to compare with others carriers. Methods Various formulations of transfersomes [The representative formulations of SHPT contained different quantity of volatile oils including SHPT-A, SHPT-B, and SHPT-C; non-PEGylated transfersomes (SHT-A and SHT-B) corresponded to SHPT-A and SHPT-B; SHDT was edge activated by sodium deoxycholate], PEGylated liposomes (SHPL), and liposomes (SHLS) were prepared by ethanol injection method. Characterization of vesicles was based on results from particle size, morphology, elasticity, and entrapment efficiency (EE) studies. Elasticity was measured by constant pressure extrusion method and EE was measured by HPLC combined with centrifugation ultrafiltration. The skin permeation test was carried out with a Franz diffusion cell fitted with excised rat skin. The effects of vesicle types (SHPT, SHDT, SHLS, and SIN-HCl aqueous solution), DSPE-PEG 2000, and volatile oil in the SHPT on percutaneous permeation of SIN-HCl were investigated. Results The SIN-HCl transfersomes and liposomes were mainly unilamellar vesicles with roundish shape and average size of 93-118 nm, without gathering property. The entrapment efficiency was of 11%-40%. The elasticity order of vesicles was SHPT-B > SHDT≈SHPT-A > SHT-B > SHT-A≈SHPL > SHLS > SHPT-C. The steady-state drug percutaneous permeation rate[J (μg·cm^-2·h^-1)] order of different vesicles was SHT-B (19.10±5.74) > SHPT-B (17.06±0.34) > SHDT (15.16±0.55) > SHT-A (10.96±0.99) > SHPT-A (9.42±1.09) > SHLS (3.90±0.67) > SHPT-C (3.51±0.37) > SIN-HCl aqueous solution (2.26±0.94). The cumulative permeated percentages[Q_e(36h)] of SHT-B and SHPT-B were (89.79±6.67)%, and (84.01±6.77)%, respectively. The Q_e(36h) of SHDT, SHLS, SHPT-C and SIN-HCl aqueous solution were (73.98±10.55)%, (20.29±3.21)%, (15.45±3.04)%, and (10.33±2.91)%, respectively. The lag time of SHPT-A, SHPT-B, SHT-A, SHT-B, and SHDT (0.3-0.6 h) were significantly reduced, compared to SHLS and SIN-HCl aqueous solution (3.5-3.8 h). Conclusion SHPT edge activated by appropriate volatile oils has good elasticity and percutaneous absorption characteristics, which is better than that of liposomes and transfersomes edge activated by sodium deoxycholate to different degrees.

浙江省医药卫生科技计划项目（2015111458）；高等学校博士学科点专项科研基金（20123322120002）